Integrated Computational modelIng of Right Heart Mechanics and Blood Flow Dynamics in Congenital Heart Disease

NCT ID: NCT03217240

Last Updated: 2017-07-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

400 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-06-05

Study Completion Date

2019-08-30

Brief Summary

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Advances in paediatric cardiology and cardiac surgery have enabled the survival of most patients born with congenital heart disease (CHD) into adulthood. Many CHD patients have undergone palliative or reparative surgery earlier in life. As patients survive into adulthood, they may need intervention or surgery for residual haemodynamic lesions. This is because they are at risk of arrhythmias secondary to structure heart disease and are susceptible to acquired heart disease. In these patients, pre-operative and post-operative evaluation of right ventricular (RV) structure (shape and volume) and function is an essential component of clinical management.

Advances have been made in cardiac imaging so that accurate assessment of the right heart chamber in terms of its structure, function and physiology is possible. However, this technology has as yet never been applied in an effort to comprehensively assess RV structure, function and physiology. Cardiac Magnetic Resonance (CMR) will be used in this comprehensive assessment of structure and function. Thus, this research will allow development of a comprehensive integrated biomedical engineering (BME) R\&D platform for in-depth study and clinical diagnosis of the RV structure-function relationship and physiology and its association with biomarker, and exercise capacity in CHD.

Detailed Description

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The incidence of Congenital Heart Disease (CHD) in live new-borns is estimated to vary from 4.1/1000 to 12.3/1000. The improvement in survival of CHD patients has led to burgeoning numbers of grown-up CHD.The majority of these CHD patients face a lifetime of problems including RV dilation, ventricular arrhythmias, and sudden cardiac death.Considering inflation to visit costs and added image technology for diagnosis, the cost of each patient is expected to increase .In contrast to adult patients with acquired heart disease, abnormalities of the RV are ubiquitous in children and adults with CHD.

Currently, clinical evaluation includes ECG and pulse oximetry alongside clinical examination. Investigation of RV anatomy and physiology is evolving from a reliance on invasive studies (right heart catheterization or RHC) to non-invasive imaging techniques such as echocardiography, nuclear scintigraphy, computed tomography, and CMR .2D echocardiography is largely operator dependent and suffers from poor inter-study reproducibility.The complex geometry of the RV makes it difficult to accurately quantify remodelling before and after intervention. Nuclear scintigraphy and computed tomography (CT) are constrained by the need for ionizing radiation as well as the poor temporal resolution of the technique.Importantly, existing CMR analytics fail to exploit the full potential of the rich CMR image dataset, and do not yield information on regional RV remodelling, muscle stiffness and blood flow characterization.

Due to the challenges mentioned above, other than RV volumes and ejection fraction, other changes in RV shape and haemodynamics have yet to be considered in the official guidelines used to define eligibility for surgery and to quantify risk of operation. It is plausible that incorporation of additional variables that more comprehensively characterizes fine alterations in RV structure, function and haemodynamics in large risk-stratification models, such as the EuroSCORE and the Society of Thoracic Surgeons' Risk Calculator, may enhance risk stratification and prognostication.

Incorporating novel exploratory RV functional indices (e.g. curvedness, area strain) and computational methods (e.g. CFD, FSI simulations), and then correlating these with clinical and cardiopulmonary exercise test outcomes will allow investigators to have established an unprecedentedly sizeable and rich clinical imaging database that serves both as a touchstone for clinical reference, as well as a repository for future exploratory research.

Investigators tend to develop a comprehensive (BME) Research and Development platform for in-depth study of RV mechanics, blood flow and function in Congenital Heart Disease.

Conditions

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Congenital Heart Disease Pulmonary Hypertension

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Congenital Heart Disease

Tetralogy of Fallot Repair/Pulmonary Hypertension Cardiac Magnetic Resonance - MRI Cardiopulmonary Exercise Test Blood Sampling for all participants

Cardiac Magnetic Resonance - MRI

Intervention Type PROCEDURE

All participants will have to undergo CMR which uses interaction of the magnetic properties of body tissues with strong magnetic fields to create images. Participants will be asked to lie on a narrow bed placed inside of a large magnet for about 1 hour. Several sets of images are needed. Participants are required to stay very still and follow the instruction of the MRI technologist who operates the machine from a room next door.

Cardiopulmonary Exercise Test

Intervention Type OTHER

Participants will be asked to undergo a cardiopulmonary exercise test (CPET). Participants will need to wear a mask. Several electrodes will be placed on the chest to record heart activity during exercise. Participants will need to pedal for at least 8-12 minutes. Pedalling will be instructed to report any symptoms such as chest discomfort, shortness of breath, leg fatigue or dizziness. A small probe will be placed on participant's finger during the test to measure the oxygen content in the blood. Immediately after exercising, participants will rest for 5-10 minutes while the blood pressure and electrocardiogram are monitored. The results will be read by a cardiologist.

Blood Sampling for all participants

Intervention Type OTHER

Serum samples will be obtained before CMR. The sample will be stored at -80 degree until assay. Investigators will perform various tests related to participants heart function

Healthy Volunteer

Cardiac Magnetic Resonance - MRI Cardiopulmonary Exercise Test Blood Sampling for all participants

Cardiac Magnetic Resonance - MRI

Intervention Type PROCEDURE

All participants will have to undergo CMR which uses interaction of the magnetic properties of body tissues with strong magnetic fields to create images. Participants will be asked to lie on a narrow bed placed inside of a large magnet for about 1 hour. Several sets of images are needed. Participants are required to stay very still and follow the instruction of the MRI technologist who operates the machine from a room next door.

Cardiopulmonary Exercise Test

Intervention Type OTHER

Participants will be asked to undergo a cardiopulmonary exercise test (CPET). Participants will need to wear a mask. Several electrodes will be placed on the chest to record heart activity during exercise. Participants will need to pedal for at least 8-12 minutes. Pedalling will be instructed to report any symptoms such as chest discomfort, shortness of breath, leg fatigue or dizziness. A small probe will be placed on participant's finger during the test to measure the oxygen content in the blood. Immediately after exercising, participants will rest for 5-10 minutes while the blood pressure and electrocardiogram are monitored. The results will be read by a cardiologist.

Blood Sampling for all participants

Intervention Type OTHER

Serum samples will be obtained before CMR. The sample will be stored at -80 degree until assay. Investigators will perform various tests related to participants heart function

Interventions

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Cardiac Magnetic Resonance - MRI

All participants will have to undergo CMR which uses interaction of the magnetic properties of body tissues with strong magnetic fields to create images. Participants will be asked to lie on a narrow bed placed inside of a large magnet for about 1 hour. Several sets of images are needed. Participants are required to stay very still and follow the instruction of the MRI technologist who operates the machine from a room next door.

Intervention Type PROCEDURE

Cardiopulmonary Exercise Test

Participants will be asked to undergo a cardiopulmonary exercise test (CPET). Participants will need to wear a mask. Several electrodes will be placed on the chest to record heart activity during exercise. Participants will need to pedal for at least 8-12 minutes. Pedalling will be instructed to report any symptoms such as chest discomfort, shortness of breath, leg fatigue or dizziness. A small probe will be placed on participant's finger during the test to measure the oxygen content in the blood. Immediately after exercising, participants will rest for 5-10 minutes while the blood pressure and electrocardiogram are monitored. The results will be read by a cardiologist.

Intervention Type OTHER

Blood Sampling for all participants

Serum samples will be obtained before CMR. The sample will be stored at -80 degree until assay. Investigators will perform various tests related to participants heart function

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

For patients with repaired tetralogy of Fallot

1. Survivors of TOF repair more than one year after repair
2. Aged: 12-80

For patients with pulmonary hypertension

1. Signed informed consent prior to initiation of any study mandated procedure
2. Age between 12 - 80 years
3. Patient with clinically suspected or known primary PH belonging to one of the following subgroups of the Updated Dana Point Clinical Classification Group 1 (at least 1 of the following a)Idiopathic (IPAH), or b)Heritable (HPAH), or c)Drug or toxin induced, or d)Associated (APAH) with one of the following: i.Connective tissue disease ii.Congenital heart disease

For Healthy volunteers

1. Aged :12-80
2. Asymptomatic and ambulant
3. Resting blood pressure \<140/90 mmHg

Exclusion Criteria

1. Non-cardiac illness with a life expectancy of less than 2 years
2. Previous heart, kidney, liver or lung transplantation
3. Contraindication to MRI examination

1. Cardiac pacemaker
2. Brain aneurysm or clips
3. Electronic implants or prosthesis
4. Eye metal foreign body injury
5. Severe claustrophobia
6. Severe renal impairment, glomerular filtration rate \<30ml/min/1.73m2
4. Pregnancy


1. History of any major medical problems, any cardiovascular disease (such as hypertension or diabetes) or significant renal or lung disease (eg.COPD, Asthma, Pneumonia,Pulmonary embolism,Pulmonary edema,Respiratory tract infection,Bronchiolitis)
2. Concurrently taking any medications for cardiovascular disease (including hypertension)
3. Heavy smoking (over 5 sticks per day or who has quit smoking in less than 12 months and had smoked over 5 sticks per day)
Minimum Eligible Age

12 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Ministry of Health, Singapore

OTHER_GOV

Sponsor Role collaborator

National Heart Centre Singapore

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Dr Zhong Liang

Role: PRINCIPAL_INVESTIGATOR

Researcher

Locations

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National University Hospital

Singapore, , Singapore

Site Status NOT_YET_RECRUITING

National Heart Centre

Singapore, , Singapore

Site Status RECRUITING

KK Women's and Children's Hospital

Singapore, , Singapore

Site Status NOT_YET_RECRUITING

Countries

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Singapore

Central Contacts

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Zhong Liang

Role: CONTACT

67042237 ext. 2237

Nurkhairunisah Abdul Rahim

Role: CONTACT

67042263 ext. 2263

Facility Contacts

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Dr Chai Ping

Role: primary

67722165 ext. 2165

Nurkhairunisah Binte Abdul Rahim

Role: primary

67042263 ext. 2263

Yin Siang Liaw

Role: backup

67042274 ext. 2274

Dr Tan Teng Hong

Role: primary

63941049 ext. 1049

References

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Douglas PS, Pontone G, Hlatky MA, Patel MR, Norgaard BL, Byrne RA, Curzen N, Purcell I, Gutberlet M, Rioufol G, Hink U, Schuchlenz HW, Feuchtner G, Gilard M, Andreini D, Jensen JM, Hadamitzky M, Chiswell K, Cyr D, Wilk A, Wang F, Rogers C, De Bruyne B; PLATFORM Investigators. Clinical outcomes of fractional flow reserve by computed tomographic angiography-guided diagnostic strategies vs. usual care in patients with suspected coronary artery disease: the prospective longitudinal trial of FFR(CT): outcome and resource impacts study. Eur Heart J. 2015 Dec 14;36(47):3359-67. doi: 10.1093/eurheartj/ehv444. Epub 2015 Sep 1.

Reference Type BACKGROUND
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PMID: 23369674 (View on PubMed)

Geva T, Sandweiss BM, Gauvreau K, Lock JE, Powell AJ. Factors associated with impaired clinical status in long-term survivors of tetralogy of Fallot repair evaluated by magnetic resonance imaging. J Am Coll Cardiol. 2004 Mar 17;43(6):1068-74. doi: 10.1016/j.jacc.2003.10.045.

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Zhao X, Lee PT, Hu L, Tan RS, Chai P, Yeo TJ, Leng S, Ouyang R, Bryant JA, Teo LLS, van der Geest RJ, Yip JW, Tan JL, Zhong Y, Zhong L. Right Ventricular Restrictive Physiology Is Associated With Right Ventricular Direct Flow From 4D Flow CMR. JACC Asia. 2024 Oct 22;4(12):912-924. doi: 10.1016/j.jacasi.2024.08.019. eCollection 2024 Dec.

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Zhao X, Tan RS, Garg P, Chai P, Leng S, Bryant JA, Teo LLS, Yeo TJ, Fortier MV, Low TT, Ong CC, Zhang S, Van der Geest RJ, Allen JC, Tan TH, Yip JW, Tan JL, Hughes M, Plein S, Westenberg JJM, Zhong L. Age- and sex-specific reference values of biventricular flow components and kinetic energy by 4D flow cardiovascular magnetic resonance in healthy subjects. J Cardiovasc Magn Reson. 2023 Sep 18;25(1):50. doi: 10.1186/s12968-023-00960-x.

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Zhao X, Hu L, Leng S, Tan RS, Chai P, Bryant JA, Teo LLS, Fortier MV, Yeo TJ, Ouyang RZ, Allen JC, Hughes M, Garg P, Zhang S, van der Geest RJ, Yip JW, Tan TH, Tan JL, Zhong Y, Zhong L. Ventricular flow analysis and its association with exertional capacity in repaired tetralogy of Fallot: 4D flow cardiovascular magnetic resonance study. J Cardiovasc Magn Reson. 2022 Jan 3;24(1):4. doi: 10.1186/s12968-021-00832-2.

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Related Links

Access external resources that provide additional context or updates about the study.

https://www.ncbi.nlm.nih.gov/pubmed/26330417

Clinical outcomes of fractional flow reserve.

https://www.ncbi.nlm.nih.gov/pubmed/22922562

Diagnostic accuracy of fractional flow reserve from anatomic CT angiography

https://www.ncbi.nlm.nih.gov/pubmed/22032711

Diagnosis of ischemia-causing coronary stenoses by noninvasive fractional flow reserve computed from coronary computed tomographic angiograms.

https://www.ncbi.nlm.nih.gov/pubmed/22922698

Guidelines on the management of valvular heart disease (version 2012): the Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS).

https://www.ncbi.nlm.nih.gov/pubmed/?term=The+effects+of+pregnancy+on+right+ventricular+remodeling+in+women+with+repaired+tetralogy+of+fallot

The effects of pregnancy on right ventricular remodeling in women with repaired tetralogy of Fallot

https://www.ncbi.nlm.nih.gov/pubmed/?term=Factors+associated+with+impaired+clinical+status+in+long-term+survivors+of+tetralogy+of+fallot+repair+evaluated+by+magnetic+resonance+imaging

Factors associated with impaired clinical status in long-term survivors of tetralogy of Fallot repair evaluated by magnetic resonance imaging

https://www.ncbi.nlm.nih.gov/pubmed/?term=Recommendations+for+cardiovascular+magnetic+resonance+in+adults+with+congenital+heart+disease+from+the+respective+working+groups+of+the+European+Society+of+Cardiology

Recommendations for cardiovascular magnetic resonance in adults with congenital heart disease from the respective working groups of the European Society of Cardiology

https://www.ncbi.nlm.nih.gov/pubmed/18046031

Computed tomography--an increasing source of radiation exposure

Other Identifiers

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NHeartCentreS

Identifier Type: -

Identifier Source: org_study_id

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